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Nutrient-Gene Interactions

Insulin-Like Growth Factor-I (IGF-I) Attenuates Jejunal Atrophy in Association with Increased Expression of IGF-I Binding Protein-5 in Parenterally Fed Mice¹

University of Wisconsin-Madison, Department of Nutritional Sciences, Madison, WI 53706

²To whom correspondence should be addressed. E-mail: ney{at}nutrisci.wisc.edu.

Total parenteral nutrition (TPN) induces dramatic mucosal hypoplasia in rat small intestine that is attenuated by insulin-like growth factor-I (IGF-I). Our aim was to determine the extent of TPN-induced intestinal atrophy and its response to infusion of IGF-I in mice. Male C57BL/6 mice (18–22 g) were maintained with TPN, TPN plus co-infusion of recombinant human IGF-I [2.5 mg/(kg · d)] or oral feeding for 5 d. Body weights did not differ among the groups although serum IGF-I was increased by 78% with IGF-I infusion. IGF-I prevented the significant 25% reduction in mass of the intact small intestine due to TPN compared with oral feeding. Greater TPN-induced atrophy was noted in duodenum and jejunum than ileum. Jejunal atrophy induced by TPN reflected significant decreases in muscularis mass and concentrations of protein and DNA; mucosal cellularity was not altered by TPN. TPN induced a significant decrease in jejunal muscularis width that was reversed by IGF-I with no differences in mucosal villus height and crypt depth. Local expression of IGF-I binding protein (IGFBP)-5 positively modulates the intestinotrophic effects of IGF-I. Jejunal atrophy due to TPN and growth due to IGF-I were directly associated with expression of IGFBP-5 mRNA. TPN decreased IGFBP-5 mRNA by 60% and IGF-I increased IGFBP-5 mRNA by 200% with no change in IGF-I mRNA compared with oral feeding. In summary, TPN induces significant 25% atrophy of the mouse small intestine that is attenuated by IGF-I in association with increased expression of IGFBP-5. Compared with rats, TPN-induced atrophy is less severe and occurs primarily in the jejunal muscularis layer in mice.

KEY WORDS: • total parenteral nutrition • jejunal mucosa and muscularis • IGF-I

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